Qi Yulin, Geib Timon, Volmer Dietrich A
Institute of Bioanalytical Chemistry, Saarland University, 66123, Saarbrücken, Germany.
J Am Soc Mass Spectrom. 2015 Jul;26(7):1143-9. doi: 10.1007/s13361-015-1118-x. Epub 2015 Apr 11.
Cyclodextrins (CDs) are a group of cyclic oligosaccharides, which readily form inclusion complexes with hydrophobic compounds to increase bioavailability, thus making CDs ideal drug excipients. Recent studies have also shown that CDs exhibit a wide range of protective effects, preventing proteins from aggregation, degradation, and folding. These effects strongly depend on the binding sites on the protein surface. CDs only exhibit weak interactions with amino acids, however; conventional analytical techniques therefore usually fail to reveal the exact location of the binding sites. Moreover, some studies even suggest that CD inclusion complexes are merely electrostatic adducts. Here, electron capture dissociation (ECD) was applied in this proof-of-concept study to examine the exact nature of the CD/peptide complexes, and CD binding sites were unambiguously located for the first time via Fourier-transform ion cyclotron resonance (FTICR) tandem mass spectrometry.
环糊精（CDs）是一类环状寡糖，它们能与疏水性化合物轻易形成包合物以提高生物利用度，因此使环糊精成为理想的药物辅料。最近的研究还表明，环糊精具有广泛的保护作用，可防止蛋白质聚集、降解和折叠。这些作用很大程度上取决于蛋白质表面的结合位点。然而，环糊精与氨基酸仅表现出微弱的相互作用；因此，传统分析技术通常无法揭示结合位点的确切位置。此外，一些研究甚至表明环糊精包合物仅仅是静电加合物。在此，本概念验证研究应用了电子捕获解离（ECD）来检查环糊精/肽复合物的确切性质，并首次通过傅里叶变换离子回旋共振（FTICR）串联质谱明确确定了环糊精的结合位点。
